Two strains of mice (C57BL/6J and DBA/2J) were used to determine the effects of single and multiple injections of methadone on open field activity and on brain monoamines. For the DBA strain, the initial injection of methadone produced an attenuation of locomotor activity. After 7 daily injections, activity increased to that of controls. For the C57 strain, the initial injection produced a slight increase in activity which became more pronounced after further daily injections. Norepinephrine concentration was elevated in brains of DBA mice chronically exposed to methadone. This effect was not observed in C57 mice nor in either strain injected only once with the drug. Serotonin concentration was not altered in animals of either strain whether acutely or chronically exposed to methadone. The results of this study suggest: 1) that activity change following methadone injections is dependent upon genetic factors and previous experience with the drug; 2) that the tolerance develops to the drug produced decreases but not increases in activity; and 3) that chronic exposure to the drug can elevate norepinephrine concentration in the brains of DBA mice.
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